This study aimed to investigate the role of the apolipoprotein ε4 allele in moderating the influence of an exogenous stressor, an earthquake, on health. A "natural experiment" design was used where the interaction between the presence of the apolipoprotein ε4 allele and the level of subjective and objective exposure to a devastating earthquake was examined in a population-based cohort of elderly Taiwanese (N = 718). The cognitive-affective dimension of health was assessed by measures of perceived control and depression and functional limitations were assessed using measures of instrumental activities of daily living and mobility. Overall health status was gauged using a single-item measure of self-rated health. Those who experienced damage to their property or were forced to move from their homes (high objective exposure) demonstrated low levels of self-rated health and somewhat lower perceived control a year later, only if they were apolipoprotein ε4 carriers. Similarly, those who found the earthquake severely distressing (high subjective exposure) were shown to have low levels of functioning and low self-rated health a year later, only if they possessed the ε4 allele. Our findings suggest that genetic variation in the apolipoprotein E gene may modify the health effects of the exogenous stress of natural disaster exposure.